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2.
Proc Natl Acad Sci U S A ; 120(9): e2219952120, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36802416

RESUMEN

Social behavior starts with dynamic approach prior to the final consummation. The flexible processes ensure mutual feedback across social brains to transmit signals. However, how the brain responds to the initial social stimuli precisely to elicit timed behaviors remains elusive. Here, by using real-time calcium recording, we identify the abnormalities of EphB2 mutant with autism-associated Q858X mutation in processing long-range approach and accurate activity of prefrontal cortex (dmPFC). The EphB2-dependent dmPFC activation precedes the behavioral onset and is actively associated with subsequent social action with the partner. Furthermore, we find that partner dmPFC activity is responsive coordinately to the approaching WT mouse rather than Q858X mutant mouse, and the social defects caused by the mutation are rescued by synchro-optogenetic activation in dmPFC of paired social partners. These results thus reveal that EphB2 sustains neuronal activation in the dmPFC that is essential for the proactive modulation of social approach to initial social interaction.


Asunto(s)
Corteza Prefrontal , Receptor EphB2 , Conducta Social , Animales , Ratones , Encéfalo , Neuronas/fisiología , Corteza Prefrontal/fisiología , Receptor EphB2/genética , Receptor EphB2/fisiología
3.
Pathol Res Pract ; 241: 154229, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36509010

RESUMEN

Advanced laryngeal squamous cell carcinoma (LSCC) has a high mortality rate, and the prognosis is poor. However, the underlying molecular biological mechanisms bringing about the development and progression of advanced LSCC are not entirely clarified. This study aimed to find out the potential biomarkers to predict the prognosis in advanced LSCC patients who had undergone postoperative radiotherapy alone. The next-generation sequencing of RNA was performed to detect the mRNAs expression profiling in 10 advanced LSCC samples, comprised of 5 samples from LSCC patients with favorable outcome and 5 samples from paired patients with poor outcome. Then bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to find out functional core genes that were significantly different between the two groups. 1630 differentially expressed genes (DEGs) were confirmed to have significant differences between the two groups. 53 GO terms and 19 pathways which were closely related to the DEGs were identified. Finally, 52 intersection DEGs which were both related to the top three GO terms and pathways were identified. The expression of several core genes was confirmed with RT-qPCR in tissues from another 75 patients. RT-qPCR confirmed that the genes of c-JUN, LYN, PIK3R2, and TNFAIP3 were significantly differentially expressed between the two groups, which was in accordance with the RNA sequencing data. The DEGs identified above may be potential prognostic markers for advanced LSCC patients with postoperative radiotherapy, and may provide essential guidance for following-up.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Pronóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , Perfilación de la Expresión Génica , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/metabolismo , Redes Reguladoras de Genes , Neoplasias de Cabeza y Cuello/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
4.
Neoplasma ; 69(3): 550-559, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35188403

RESUMEN

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck cancer, with a poor prognosis. As we know, microRNAs (miRNAs) play a vital role in the initiation and development of various cancers including LSCC. In this study, we explored the role of miR-125b-5p and its downstream regulatory pathway in LSCC. Our data demonstrated that miR-125b-5p expression was significantly downregulated in LSCC tissues and cells. LSCC patients with high expression of miR-125b-5p had higher overall survival (OS) and were closely related to the clinical stage. Overexpression of miR-125b-5p impaired viability and glycolysis, and facilitated apoptosis in LSCC cells. And miR-125b-5p silencing had the opposite effects. Bioinformatics website predicted that MAP3K9 was one of the potential target genes of miR-125b-5p. Cell experiments demonstrated that miR-125b-5p repressed the MAP3K9 levels by directly targeting MAP3K9. Additionally, the negative correlation between miR-125b-5p and MAP3K9 was validated in LSCC tissues. Overexpression of MAP3K9 attenuated the inhibitory effect of miR-125b-5p on viability and glycolysis, and the pro-apoptosis effect of miR-125b-5p in LSCC cells. Furthermore, in vivo experiments demonstrated that tumor growth was hampered in AMC-HN-8 cells transfected with miR-125b-5p mimic. In contrast, the knockdown of miR-125b-5p reduced tumor growth in vivo. Meanwhile, the in vivo immunohistochemistry and TUNEL assays suggested that the miR-125b-5p overexpression restrained cell proliferation and promoted apoptosis via targeting MAP3K9. Overall, these above results suggested that miR-125b-5p suppressed proliferation and glycolysis, and promoted apoptosis by directly targeting MAP3K9 in LSCC cells. Thus, miR-125b-5p acts as a tumor suppressor miRNA and the miR-125b-5p/MAP3K9 axis may be a promising candidate for LSCC treatment.


Asunto(s)
Neoplasias Laríngeas , Quinasas Quinasa Quinasa PAM , MicroARNs , Carcinoma de Células Escamosas de Cabeza y Cuello , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , Neoplasias Laríngeas/patología , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , MicroARNs/biosíntesis , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico
5.
Exp Ther Med ; 22(3): 1007, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34345289

RESUMEN

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with increasing incidence and poor prognosis. Circular RNAs (circRNAs) are known to modulate tumorigenesis and cancer development that may function through microRNAs (miRs). The aim of the present study was to investigate the functional roles of circ_0001883 in LSCC and the underlying molecular mechanism. The expression of circ_0001883 was upregulated and measured using reverse transcription-quantitative PCR (RT-qPCR) and RNase R. miR-125b-5p expression was downregulated in LSCC tissues and cells as determined using RT-qPCR. Subsequently, knockdown of circ_0001883 inhibited LSCC cell migration, invasion and epithelial-mesenchymal transition (EMT), which were tested by wound healing assays, Transwell assays and western blotting, respectively. Bioinformatics analysis predicted that circ_0001883 was a sponge of miR-125b-5p, which was verified using a dual-luciferase reporter assay. Knockdown of circ_0001883 played a functional role by sponging miR-125b-5p. Additionally, circ_0001883 and miR-125b-5p influenced phosphorylation of PI3K and AKT, detected via western blotting. In an in vivo study, knockdown of circ_0001883 reduced tumor volume and weight in mice, along with enhanced miR-125b-5p and E-cadherin expression levels, and decreased N-cadherin, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT ratios. In conclusion, knockdown of circ_0001883 inhibited cell migration, invasion and EMT of LSCC by sponging miR-125b-5p. This is hypothesized to be via the PI3K/AKT signaling pathway, which suggested that circ_0001883 has potential for LSCC therapy.

6.
Technol Cancer Res Treat ; 20: 15330338211019511, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34044671

RESUMEN

OBJECTIVE: In this study, by comparing coplanar and noncoplanar intensity-modulated radiation therapy (IMRT) treatment planning in treating tongue cancer, the significance of noncoplanar fields in the protection of the lip and buccal mucosa was determined, and a reasonable solution was selected. METHODS: Forty-eight tongue cancer patients treated from June 2019 to February 2021 were selected and randomly divided into a coplanar field group and a noncoplanar field group. The mucosal dose limit changed from 15 Gy to 45 Gy for comparison of the two treatment plans. The evaluation indicators (conformal index (CI); homogeneity index (HI); D5, D50, and D98 of the target volume; and the dose of normal tissues) were calculated under different mucosal dose limits. The clinical observation of the lip and buccal mucosa of 48 cases was monitored and graded carefully according to NCI-CTCAE V4.0. Statistical analyses were performed. RESULTS: The differences in CI, HI, D98, D50 and D5 between the two groups in the target volume tended to decrease when the mucosal dose limit was less than 30 Gy, with a significant difference (P < 0.05). When the limit exceeded 30 Gy, significant differences in other indicators except CI (P < 0.05) were still noted. In normal tissue, differences in doses between the two groups existed when the mucosal limit was less than 20 Gy, with a significant difference (P < 0.05). When the limit exceeded 20 Gy, no significant difference was noted. Patients in the noncoplanar group showed significantly better results than those in the other group in terms of the radiation-related toxicity of the lip and cheek membrane(P < 0.001). CONCLUSIONS: Compared with coplanar field radiotherapy, noncoplanar field radiotherapy can effectively reduce the exposure dose to the lip and buccal mucosa. The application of noncoplanar treatment plans exhibits good clinical significance and deserves to be promoted.


Asunto(s)
Labio/efectos de la radiación , Mucosa Bucal/efectos de la radiación , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Neoplasias de la Lengua/radioterapia , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Neoplasias de la Lengua/patología
7.
PLoS One ; 10(7): e0133895, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26208323

RESUMEN

Diagnostic and prognostic indicators are key components to achieve the goal of personalized cancer therapy. Two distinct approaches to this goal include predicting response by genetic analysis and direct testing of possible therapies using cultures derived from biopsy specimens. Optimally, the latter method requires a rapid assessment, but growing xenograft tumors or developing patient-derived cell lines can involve a great deal of time and expense. Furthermore, tumor cells have much different responses when grown in 2D versus 3D tissue environments. Using a modification of existing methods, we show that it is possible to make tumor-fragment (TF) spheroids in only 2-3 days. TF spheroids appear to closely model characteristics of the original tumor and may be used to assess critical therapy-modulating features of the microenvironment such as hypoxia. A similar method allows the reproducible development of spheroids from mixed tumor cells and fibroblasts (mixed-cell spheroids). Prior literature reports have shown highly variable development and properties of mixed-cell spheroids and this has hampered the detailed study of how individual tumor-cell components interact. In this study, we illustrate this approach and describe similarities and differences using two tumor models (U87 glioma and SQ20B squamous-cell carcinoma) with supporting data from additional cell lines. We show that U87 and SQ20B spheroids predict a key microenvironmental factor in tumors (hypoxia) and that SQ20B cells and spheroids generate similar numbers of microvesicles. We also present pilot data for miRNA expression under conditions of cells, tumors, and TF spheroids.


Asunto(s)
Neoplasias/genética , Neoplasias/patología , Esferoides Celulares , Biomarcadores , Línea Celular Tumoral , Fibroblastos , Humanos , MicroARNs , Neovascularización Patológica , Células del Estroma , Células Tumorales Cultivadas , Microambiente Tumoral
8.
Eur Arch Otorhinolaryngol ; 271(3): 445-54, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23475101

RESUMEN

The aim of this study was to examine and assess comparative values of HRCT-based multiplanar reformation (MPR), volume rendering (VR) and virtual endoscope built on three-dimensional (3D) shaded-surface display (SSD-based CTVE) for detections of ossicular chain's damage in patients with otitis media. 70 human ears from 70 patients suffering by chronic otitis media or cholesteatoma, who were examined with a preoperative multi-slice computer tomography (MSCT) examination and tympanoplasty in our hospital were collected. The patients ossicular chains were reconstructed with the aforementioned three protocols and assessed via a three-point scoring system by three radiologists. Then, all the patients ossicular chains were reviewed by a surgeon and a radiologist via the same three-point scoring system used during surgeries at same time. By calculation, the Youden's index and coincidence rate were acquired without a significant difference for display of malleus. With regard to the incus, the Youden's index and coincidence rate of VR and MPR did not show any difference, however, both were higher than CTVE. For representation of the stapes, the accuracy of these three modalities is very low; especially, for the CTVE. In conclusion, both MPR and VR are relative robust, and CTVE is not effective for evaluation of small ossicular structures, particularly the stapes. Furthermore, the VR images are real 3D ones. Therefore, it could be the more valuable protocols for detection of the damage of ossicular chain in the patients with otitis media, and should be further applied in the future work.


Asunto(s)
Colesteatoma del Oído Medio/diagnóstico por imagen , Osículos del Oído/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada Multidetector/métodos , Otitis Media Supurativa/diagnóstico por imagen , Adolescente , Adulto , Niño , Colesteatoma del Oído Medio/cirugía , Enfermedad Crónica , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Otitis Media Supurativa/cirugía , Cuidados Preoperatorios , Timpanoplastia/métodos , Adulto Joven
9.
Otolaryngol Head Neck Surg ; 147(3): 535-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22467283

RESUMEN

Labyrinthine sequestrum, a rare form of labyrinthitis, is highly distinct from the more commonly encountered labyrinthitis ossificans based on its unique clinical, radiologic, and histologic characteristics. The study included 4 such patients who had undergone clinical and laboratory investigations, computed tomography (CT), and magnetic resonance imaging (MRI) assessments followed by surgical procedures and pathological evaluation. Their major symptoms were otorrhea, otalgia, tinnitus, and profound hearing loss. Imaging studies showed an osteolytic soft mass with calcified debris in the inner ear, and the bony labyrinth was eroded partly or completely by granulation mass, with loss of bony morphology. Further pathological examination was coincident with inflammatory granulation tissue with some calcification or osseous tissue. The disease process is attributed to chronic osteomyelitis due to the presence of osteonecrosis. Prompt CT and MRI examinations and optimal therapeutic management facilitate definitive diagnosis and protect against fatal complications.


Asunto(s)
Laberintitis/diagnóstico , Imagen por Resonancia Magnética , Osteomielitis/diagnóstico , Tomografía Computarizada por Rayos X , Adulto , Calcinosis/diagnóstico , Calcinosis/patología , Calcinosis/cirugía , Oído Interno/patología , Oído Interno/cirugía , Femenino , Estudios de Seguimiento , Tejido de Granulación/patología , Tejido de Granulación/cirugía , Humanos , Laberintitis/patología , Laberintitis/cirugía , Masculino , Osteólisis/diagnóstico , Osteólisis/patología , Osteólisis/cirugía , Osteomielitis/patología , Osteomielitis/cirugía , Osteonecrosis/diagnóstico , Osteonecrosis/patología , Osteonecrosis/cirugía
12.
Chin Med J (Engl) ; 120(20): 1777-82, 2007 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-18028770

RESUMEN

BACKGROUND: Drug treatment for secondary hyperparathyroidism caused by chronic renal failure may be available at the early stage of the disease, but it is not as effective for serious patients. The aim of the study was to evaluate the effect of total parathyroidectomy combined with forearm autotransplantation in the uremic patients with secondary hyperparathyroidism. METHODS: From September 1999 through September 2006, parathroidectomy and autotransplantation was performed in 20 patients. The coherence between the results of preoperative parathyroid ultrasonography and surgical exploration were compared. The serum calcium concentration and intact parathyroid hormone (iPTH) were monitored preoperatively, intraoperatively, and postoperatively. RESULTS: A total of 71 hyperplastic parathyroid glands were resected in the 20 patients. The accordance rate of parathyroid localization between B-ultrasonography and intraoperative exploration was 94.4%. The average iPTH value was (110.90 +/- 67.42) ng/L, (433.80 +/- 243.72) ng/L, (48.80 +/- 42.69) ng/L, (229.04 +/- 172.68) ng/L and (232.39 +/- 224.05) ng/L at day 1, 2, 3, 7, 30 after operation respectively. The clinical symptoms were ameliorated and the levels of serum calcium concentration were controlled within the normal range after operation. Recurrent secondary hyperparathyroidism had happened in 1 case, 4 years postoperatively because of the development of autograft hyperplasia, and in another case 2 years postoperatively due to remnant of neck parathyroid glands. The clinical symptoms were all alleviated after re-operation. No surgical complication had occurred in any of the patients. CONCLUSIONS: The total parathyroidectomy with forearm autotransplantation is feasible, safe, and effective for patients with secondary hyperparathyroidism in the short term. The long-term effects should be further investigated.


Asunto(s)
Hiperparatiroidismo Secundario/cirugía , Glándulas Paratiroides/trasplante , Paratiroidectomía/métodos , Adulto , Anciano , Calcio/sangre , Femenino , Estudios de Seguimiento , Antebrazo , Humanos , Hiperparatiroidismo Secundario/sangre , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/diagnóstico por imagen , Hormona Paratiroidea/sangre , Trasplante Autólogo , Ultrasonografía
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